Markers for the prognosis and risk assessment of pregnancy-induced hypertension and preeclampsia

Abstract

The present invention relates to the prognosis and risk assessment in pregnant women to develop pregnancy-induced hypertension and/or preeclampsia by the determination of marker levels.

1 . A method for the prognosis of development of pregnancy-induced hypertension and/or preeclampsia or risk assessment in pregnant women to develop pregnancy-induced hypertension and/or preeclampsia comprising the steps of:
 (i) providing a sample of a bodily fluid of a subject,   (ii) determining the level of pro-ADM or fragments thereof and/or pro-ET-1 or fragments thereof in said sample,   (iii) correlating the level of pro-ADM or fragments thereof and/or pro-ET-1 or fragments thereof with the prognosis or risk assessment for a pregnant woman,   wherein said fragments have a lengths of at least 6 amino acid residues.   
     
     
         2 . The method of  claim 1 , wherein the determination of the level pro-ADM or fragments thereof and/or pro-ET-1 or fragments thereof is carried out within the first to second trimester (8 th  to 26 th  week of pregnancy), more preferred within the first to early second trimester (8 th  to 20 th  week of pregnancy), even more preferred within the first trimester (8 th  to 14 th  week of pregnancy), mostly preferred within the early first trimester (8 th  to 10 th  week of pregnancy). 
     
     
         3 . The method of  claim 1 , wherein the prognosis or risk assessment is related to an early onset (between 20 to 34 weeks of gestation) or a late onset (after 34 weeks of gestation) of preeclampsia. 
     
     
         4 . The method of  claim 1 , wherein at least one further marker selected from the group sflt-1, sEng, PIGF, VEGF, PP-13, ADAM12, P-Selectin, cell-free fetal DNA, PTX3, PAPP-A, Visfatin, inhibin A, activin A, human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), metalloproteinase-9 (MMP-9), ultrasound markers (uterine artery pulsatility index and/or diastolic notching), pro-atrial natriuretic peptide (proANP) or fragments thereof, pro-brain natriuretic peptide (proBNP) or fragments thereof and pro-Vasopressin or fragments thereof is determined. 
     
     
         5 . The method of  claim 1 , wherein the level of MR-pro-ADM and/or CT-pro-ET-1 is determined. 
     
     
         6 . The method of  claim 1 , wherein the determination of the level of MR-pro-ADM and/or CT-pro-ET-1 is combined with PAPP-A, PLGF and/or ultrasound markers (uterine artery pulsatility index and/or diastolic notching). 
     
     
         7 . The method of  claim 1 , wherein pregnancy-induced hypertension and/or preeclampsia is asymptomatic and/or not manifested in said pregnant woman at the time of measuring. 
     
     
         8 . The method of  claim 1 , wherein said sample is a bodily fluid, in particular blood, serum, plasma, cerebrospinal fluid, urine, saliva or a pleural effusion. 
     
     
         9 . The method of  claim 1 , wherein the predetermined threshold level of MR-pro-ADM is between 0.2 and 0.6 nmol/L, more preferably between 0.2 nmol/L and 0.5 nmol/L, even more preferred between 0.2 nmol/L and 0.4 nmol/L, most preferred between 0.2 nmol/L and 0.3 nmol/L. 
     
     
         10 . The method of  claim 1 , wherein the predetermined threshold level of CT-pro-ET-1 is between 20 and 60 pmol/L, more preferably between 20 pmol/L and 50 pmol/L, even more preferred between 20 pmol/L and 40 pmol/L, most preferred between 20 pmol/L and 30 pmol/L. 
     
     
         11 . The method of  claim 1 , wherein the development of a pregnancy-induced hypertension and/or preeclampsia is predicted in a pregnant woman when said determined level of MR-pro-ADM or CT-pro-ET-1 is lower than the predetermined threshold level.